Andrews David M, Gibson Keith M, Graham Mark A, Matusiak Zbigniew S, Roberts Craig A, Stokes Elaine S E, Brady Madeleine C, Chresta Christine M
Cancer and Infection Research, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.
Bioorg Med Chem Lett. 2008 Apr 15;18(8):2525-9. doi: 10.1016/j.bmcl.2008.03.058. Epub 2008 Mar 22.
A lead benzamide, bearing a cyanopyridyl moiety (3), was identified as a potent and low molecular weight histone deacetylase (HDAC) inhibitor. Various replacements of the cyano group were explored at the C3-position, along with the exploration of solubility-enhancing groups at the C5-position. It was determined that cyano substitution at the C3-position of the pyridyl core, along with a methylazetidinyl substituent at the C5-position yielded optimal HDAC1 inhibition and anti-proliferative activity in HCT-116 cells.
一种带有氰基吡啶部分的苯甲酰胺（3）被鉴定为一种强效且低分子量的组蛋白脱乙酰酶（HDAC）抑制剂。在C3位探索了氰基的各种取代基，同时在C5位探索了增强溶解性的基团。已确定吡啶核心C3位的氰基取代以及C5位的甲基氮杂环丁烷基取代基在HCT-116细胞中产生了最佳的HDAC1抑制和抗增殖活性。
